Neuroscience
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In brainstem motor networks, hypoglossal motoneurons (HMs) play the physiological role of driving tongue contraction, an activity critical for inspiration, phonation, chewing and swallowing. HMs are an early target of neurodegenerative diseases like amyotrophic lateral sclerosis that, in its bulbar form, is manifested with initial dysphagia and dysarthria. One important pathogenetic component of this disease is the high level of extracellular glutamate due to uptake block that generates excitotoxicity. ⋯ Two hours later, propofol prevented the rise in reactive oxygen species (ROS) and, at 4 hours, it inhibited intracellular release of apoptosis-inducing factor (AIF) and prevented concomitant cell loss. Midazolam did not contrast ROS and AIF release. The present work provides experimental evidence for the neuroprotective action of a general anesthetic like propofol, which, in this case, may be achieved through a combination of boosted GABAergic inhibition and reduced ROS production.
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Parkinson's disease is a common, debilitating, neurodegenerative disorder for which the current gold standard treatment, levodopa (L-DOPA) is symptomatic. There is an urgent, unmet need for neuroprotective or, ideally, neuro-restorative drugs. We describe a 6-hydroxydopamine (6-OHDA) zebrafish model to screen drugs for neuroprotective and neuro-restorative capacity. ⋯ Importantly, they also reversed the locomotor deficit caused by prior exposure to 6-OHDA; rasagiline also reversed neuronal loss and minocycline partially restored neuronal loss due to prior 6-OHDA, making them candidates for investigation as neuro-restorative treatments for Parkinson's disease. Our findings in zebrafish reflect preliminary clinical findings for rasagiline and minocycline. Thus, we have developed a zebrafish model suitable for high-throughput screening of putative neuroprotective and neuro-restorative therapies for the treatment of Parkinson's disease.
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Oxytocin (OT) administration in the ventromedial hypothalamic nucleus (VMH) reduces chow intake. The nature of VMH OT's anorexigenic action remains unclear. Here we provide insight into neural mechanisms underlying VMH OT-driven anorexia by (a) identifying feeding-related brain sites activated by VMH OT injection; (b) measuring VMH OT receptor (OTr) mRNA changes in response to hunger and palatability; and (c) examining how VMH OT affects episodic sweet solution intake in sated and hungry rats. ⋯ OT acting in the VMH decreases intake driven by energy not by palatability, and it stimulates activity of hypothalamic sites controlling energy balance.
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Sex differences in social cognitive ability are well established, including measures of Theory of Mind (ToM). The aim of this study was to investigate if sex mediates the effects of high-definition transcranial direct current stimulation (HD-tDCS) administered to a key hub of the social brain (i.e., the dorsomedial prefrontal cortex, dmPFC) on the Reading the Mind in the Eyes Test (RMET). Forty healthy young adults (18-35 years) were randomly allocated to receive either anodal or cathodal HD-tDCS in sham HD-tDCS controlled, double blind designs. ⋯ The current study is the first to show improved performance on the RMET after tDCS to the dmPFC in females only. The polarity-specific effects and use of focal HD-tDCS provide evidence for sex-dependent differences in dmPFC function in relation to the RMET. Future studies using tDCS to study or improve ToM, need to consider sex.
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Learning a motor task in one condition typically generalizes to another, although it is unclear why it generalizes substantially in certain situations, but only partially in other situations (e.g., across movement directions and motor effectors). Here, we demonstrate that generalization of motor learning across directions and effectors can be enhanced substantially by inducing use-dependent learning, that is, by having subjects experience motor actions associated with a desired trajectory repeatedly during reaching movements. In Experiments 1 and 2, healthy human adults adapted to a visuomotor rotation while concurrently experiencing repetitive passive movements guided by a robot. ⋯ This intervention resulted in increased motor-evoked potentials (MEPs) and decreased short-interval intracortical inhibition (SICI) in the rTMS group, but not in the sham group. These changes observed in the rTMS group were accompanied by enhanced generalization of visuomotor adaptation across the arms, which was not the case in the sham group. Collectively, these findings confirm the involvement of M1 in use-dependent learning, and suggest that use-dependent learning can contribute not only to motor learning, but also to motor generalization.